1. Field of the Invention
This invention relates to a process for providing N-acyl-L-methionine and L-methionine.
2. The Prior Art
Heretofore it was known that N-acyl-D,L-methionine could be separated into its optical antipodes by reacting it with certain optically active bases, for example, threo-2-amino-(p-methylsulfonylphenyl)-1,3-propanediol, brucine, fenchylamine or lysine and to separate diastereomer salts from each other on the basis of their different physical properties, especially their different solubilities. (See, for example, U.S. Pat. No. 3,845,110 issued Oct. 29, 1974 to Fahnenstich et al.) These optically active bases, however, are themselves difficult to obtain. In addition, such processes generally do not provide good yields of high purity N-acyl-L-methionine.
Heretofore, enzymes which selectively act on particular amino acid derivatives have been employed to provide optically active amino acids. For example, U.S. Pat. No. 3,386,888, issued June 4, 1968 to Chibata et al. discloses that L-methionine can be recovered by action of acylase on N-acyl-D,L-methionine. This enzymatic method, however, is not completely desirable. The acylase employed is expensive; the rate at which the reaction proceeds is relatively slow; and acylase enzyme is unstable.
The action of pancreas extract (which contains a mammalian derived serine proteinase) on D,L-methionine isopropyl ester can provide at least a partial resolution of methionine. See, Brenner, et al., Helv. Chim. Acta, Vol. 32, pages 333-37 (1949), and Wretlind, Acta physiol. Scan., Vol. 20, page 1 (1950). Mammalian derived enzymes, however, are expensive and these publications suggest that good optical purity is not obtained. These publications, therefore, do not suggest a commercially desirable process for providing L-methionine.
It is known that microbially derived serine proteinases, for example, Novo and Carlsberg subtilisins, exhibit varying degrees of esterase activity on various N-acyl-L-amino acid esters. See, for example, Barel et al., The Jour. of Biolog. Chem., Vol. 243, pages 1344-48 (1968) and Morihara et al., Arch. Biochem. and Biophy., Vol. 129, pages 620-633 (1969). These publications show that serine proteinases exhibit high esterase activity on some of these amino acid derivatives and little or no esterase activity on others depending on the particular amino acid. These publications do not disclose the activity of serine proteinases on N-acyl-L-methionine esters, or the activity of serine proteinases on racemic N-acyl-D,L-amino acid esters.
Both L-methionine and N-C.sub.1-9 acyl-L-methionine are valuable nutritional supplements, therefore a more effective process for obtaining these nutritionally valuable compounds would be very desirable. An especially effective process would (1) involve readily available and inexpensive materials (e.g. enzymes), and (2) produce high purity material in high yield at a rapid rate.